你或许不知道，牛虻唾液腺中含有丰富的抗血栓活性物质。近几年来，中国科学院昆明动物研究所赖仞研究员领导的学科组从牛虻唾液腺中识别了大量的抗血栓功能物质。
近日，该研究团队在以前工作的基础上与美国NIH John博士领导的团队合作研究发现，牛虻唾液腺中的一个血小板聚集抑制因子含有一独特的空间结构域，该结构域既是血小板膜受体aIIbb3的结合位点，同时也结合类十二烷酸物质。类十二烷酸包括血栓烷、白三烯、前列腺环素和前列腺素等4大类物质，具有导致血管收缩、发炎等生物功能，是导致血栓、血管硬化的重要因素。目前的研究结果表明，该双功能蛋白不仅可以通过抑制血小板功能，同时也以通过清除类十二烷酸来达到抗血栓的目的。
可同时结合血小板膜受体和类十二烷酸的双功能结构域的识别为开发高效抗血栓药物提供了先导模板。相关论文发表在该研究成果已发表于国际学术期刊JBC上。（生物谷Bioon.com）
doi:10.1074/jbc.M112.340471
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Structure of Protein Having Inhibitory Disintegrin and Leukotriene Scavenging Functions Contained in Single Domain
Xueqing Xu, Ivo M. B. Francischetti, Ren Lai§, José M. C. Ribeiro and John F. Andersen
The antihemostatic/antiangiogenic protein tablysin-15 is a member of the CAP (cysteine-rich secretory, antigen 5, and pathogenesis-related 1 protein) superfamily and has been shown to bind the integrins αIIbβ3 and αVβ3 by means of an Arg-Gly-Asp (RGD) tripeptide sequence. Here we describe the x-ray crystal structure of tablysin-15 and show that the RGD motif is located in a novel structural context. The motif itself is contained in a type II β-turn structure that is similar in its conformation to the RGD sequence of the cyclic pentapeptide cilengitide when bound to integrin αVβ3. The CAP domain also contains a hydrophobic channel that appears to bind a fatty acid molecule in the crystal structure after purification from Escherichia coli. After delipidation of the protein, tablysin-15 was found to bind proinflammatory cysteinyl leukotrienes with submicromolar affinities. The structure of the leukotriene E4-tablysin-15 complex shows that the ligand binds with the nonfunctionalized end of the fatty acid chain buried in the hydrophobic pocket, whereas the carboxylate end of the ligand binds forms hydrogen bond/salt bridge interactions with polar side chains at the channel entrance. Therefore, tablysin-15 functions as an inhibitor of integrin function and as an anti-inflammatory scavenger of eicosanoids.
